284 REACTIONSOFARENES:ELECTROPHILIC AROMATIC SUBSTITUTION positions of the ring that are activated by the methoxy group in p-methoxyacetophenone ar (d) A methoxy group is ortho, para-directing, and a carbonyl group is meta-directing. The op lso those that are meta to the carbonyl, so the directing effects of the two substituents reinforce each other. Nitration of p-methoxyacetophenone yields 4-methoxy-3-nitroacetophenone CHC HOCH OCH3 (e) The methoxy group of p-methylanisole activates the positions that are ortho to it; the methyl se ortho to so nitration occurs ortho to the methoxy group -OCH3 OCH Methyl activates C-3 and C-5 4-Methyl-2-nitroanisole (f) All the substituents in 2,6-dibromoanisole are ortho, para-directing, and their effects are felt at different positions. The methoxy group, however, is a far more powerful activating substituent than bromine, so it controls the regioselectivity of nitration OCH OCH Methoxy directs toward C-4 2.6-Dibromo 4nitroanisole bromines direct toward C-3 and C-5 12.18 The product that is obtained when benzene is subjected to bromination and nitration depends on the order in which the reactions are carried out. A nitro is meta-directing, and so if it is introduced prior to the bromination step, m-bromonitrobenzene is obtained. HNO, H,SO m- Bromonitrobenzene Bromine is an ortho, para-directing group. If it is introduced first, nitration of the resulting bromobenzene yields a mixture of o-bromonitrobenzene and p-bromonitrobenzene Br O2 HSO o-Bromonitrobenzene p-Bromonitrobenzene Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
(d) A methoxy group is ortho, para-directing, and a carbonyl group is meta-directing. The open positions of the ring that are activated by the methoxy group in p-methoxyacetophenone are also those that are meta to the carbonyl, so the directing effects of the two substituents reinforce each other. Nitration of p-methoxyacetophenone yields 4-methoxy-3-nitroacetophenone. (e) The methoxy group of p-methylanisole activates the positions that are ortho to it; the methyl activates those ortho to itself. Methoxy is a more powerful activating substituent than methyl, so nitration occurs ortho to the methoxy group. ( f ) All the substituents in 2,6-dibromoanisole are ortho, para-directing, and their effects are felt at different positions. The methoxy group, however, is a far more powerful activating substituent than bromine, so it controls the regioselectivity of nitration. 12.18 The product that is obtained when benzene is subjected to bromination and nitration depends on the order in which the reactions are carried out. A nitro group is meta-directing, and so if it is introduced prior to the bromination step, m-bromonitrobenzene is obtained. Bromine is an ortho, para-directing group. If it is introduced first, nitration of the resulting bromobenzene yields a mixture of o-bromonitrobenzene and p-bromonitrobenzene. Br2 FeBr3 HNO3 H2SO4 Benzene Br Bromobenzene Br NO2 o-Bromonitrobenzene Br NO2 p-Bromonitrobenzene Benzene Nitrobenzene m-Bromonitrobenzene Br NO2 NO2 HNO3 H2SO4 Br2 FeBr3 OCH3 Br Br 1 2 3 4 5 6 OCH3 NO2 Br Br Methoxy directs toward C-4; bromines direct toward C-3 and C-5. 2,6-Dibromo-4-nitroanisole (principal product of nitration) 4-Methyl-2-nitroanisole (principal product of nitration) CH3 OCH3 NO2 Methyl activates C-3 and C-5; methoxy activates C-2 and C-6. CH3 OCH3 1 6 5 4 3 2 Positions ortho to the methoxy group are meta to the carbonyl. CH3C OCH3 O 4-Methoxy-3-nitroacetophenone CH3C OCH3 O NO2 284 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 285 12.19 A straightforward approach to the synthesis of m-nitrobenzoic acid involves preparation of ben- zoic acid by oxidation of toluene, followed by nitration. The carboxyl group of benzoic acid meta-directing. Nitration of toluene prior to oxidation would lead to a mixture of ortho and para COH COH HNO HaSO Toluene Benzoic acid Im- Nitrobenzoic acid 12.20 The text points out that C-1 of naphthalene is more reactive than C-2 toward electrophilic aromatic substitution. Thus, of the two possible products of sulfonation, naphthalene-1-sulfonic acid should be formed faster and should be the major product under conditions of kinetic control. Since the problem states that the product under conditions of thermodynamic control is the other isomer, naphthalene-2-sulfonic acid is the major product at elevated temperature SO,H + aphthalene-l-sulfonic acid ct at 160°C formed faster stable bi one shown in us sulfonic acid is the more stable isomer for steric reasons. The hNyygor at C-8(the 12.21 The text states that electrophilic aromatic substitution in furan d pyrrole occurs at H,SO, 12.22 (a) Nitration of benzene is the archetypical electrophilic aromatic substitution reaction N (b) Nitrobenzene is much less reactive than benzene toward electrophilic aromatic substitution The nitro group on the ring is a meta director NO H,SO Nitrobenzene m-Dinitrobenzene Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
12.19 A straightforward approach to the synthesis of m-nitrobenzoic acid involves preparation of benzoic acid by oxidation of toluene, followed by nitration. The carboxyl group of benzoic acid is meta-directing. Nitration of toluene prior to oxidation would lead to a mixture of ortho and para products. 12.20 The text points out that C-1 of naphthalene is more reactive than C-2 toward electrophilic aromatic substitution. Thus, of the two possible products of sulfonation, naphthalene-1-sulfonic acid should be formed faster and should be the major product under conditions of kinetic control. Since the problem states that the product under conditions of thermodynamic control is the other isomer, naphthalene-2-sulfonic acid is the major product at elevated temperature. Naphthalene-2-sulfonic acid is the more stable isomer for steric reasons. The hydrogen at C-8 (the one shown in the equation) crowds the group in naphthalene-1-sulfonic acid. 12.21 The text states that electrophilic aromatic substitution in furan, thiophene, and pyrrole occurs at C-2. The sulfonation of thiophene gives thiophene-2-sulfonic acid. 12.22 (a) Nitration of benzene is the archetypical electrophilic aromatic substitution reaction. (b) Nitrobenzene is much less reactive than benzene toward electrophilic aromatic substitution. The nitro group on the ring is a meta director. HNO3 H2SO4 NO2 Nitrobenzene NO2 NO2 m-Dinitrobenzene HNO3 H2SO4 Benzene NO2 Nitrobenzene S S SO3H H2SO4 Thiophene Thiophene-2- sulfonic acid SO3H H2SO4 Naphthalene Naphthalene-1-sulfonic acid major product at 0C; formed faster H 1 2 H SO3H Naphthalene-2-sulfonic acid major product at 160C; more stable H SO3H Na2Cr2O7 H2O, H2SO4, heat HNO3 H2SO4 CH3 Toluene CO2H Benzoic acid CO2H NO2 m-Nitrobenzoic acid REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 285 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
286 REACTIONSOFARENES:ELECTROPHILIC AROMATIC SUBSTITUTION (c) Toluene is more reactive than benzene in electrophilic aromatic substitution. A methyl sub CH3 Br Toluene romotoluene p-Bromotoluene (d) Trifluoromethyl is deactivating and meta-directing. FeBr TRifluoromethyl)- m-Bromo(trifluoromethyl)- enze (e) Anisole is ortho, para-directing, strongly activated toward electrophilic aromatic substitution and readily sulfonated in sulfuric acid OCH OCH OCH H,SOA SO,H Sulfur trioxide could be added to the sulfuric acid to facilitate reaction. The para isomer is the omina (f) Acetanilide is quite similar to anisole in its behavior toward electrophilic aromatic substitution HNCCH HNCCH HNCCH SOH SO,H o-Acemlfmiobciene. p-Acetamidobenzene- sulfonic acid (g) Bromobenzene is less reactive than benzene. a bromine substituent is ortho, para-directing Bromobenzene Bromochloro- p-Bromochloro- Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
(c) Toluene is more reactive than benzene in electrophilic aromatic substitution. A methyl substituent is an ortho, para director. (d) Trifluoromethyl is deactivating and meta-directing. (e) Anisole is ortho, para-directing, strongly activated toward electrophilic aromatic substitution, and readily sulfonated in sulfuric acid. Sulfur trioxide could be added to the sulfuric acid to facilitate reaction. The para isomer is the predominant product. ( f ) Acetanilide is quite similar to anisole in its behavior toward electrophilic aromatic substitution. (g) Bromobenzene is less reactive than benzene. A bromine substituent is ortho, para-directing. FeCl3 Cl2 Br Bromobenzene Br Cl o-Bromochlorobenzene Br Cl p-Bromochlorobenzene H2SO4 HNCCH3 O Acetanilide HNCCH3 O SO3H o-Acetamidobenzenesulfonic acid HNCCH3 O SO3H p-Acetamidobenzenesulfonic acid H2SO4 OCH3 Anisole OCH3 SO3H o-Methoxybenzenesulfonic acid p-Methoxybenzenesulfonic acid OCH3 SO3H Br2 FeBr3 CF3 (Trifluoromethyl)- benzene CF3 Br m-Bromo(trifluoromethyl)- benzene Br2 FeBr3 CH3 Toluene CH3 Br o-Bromotoluene p-Bromotoluene CH3 Br 286 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 287 (h) Anisole is a reactive substrate toward Friedel-Crafts alkylation and yields a mixture of o-and p-benzylated products when treated with benzyl chloride and aluminum chloride OCH CH,CI CH,C6H5 Benzyl chloride Benzy anisole (i) Benzene will undergo acylation with benzoyl chloride and aluminum chloride o A benzoyl substituent is meta-directing and deactivating HNO Benzophenone k) Clemmensen reduction conditions involve treating a ketone with zinc amalgam and concen- Benzophenone Diphenylmethane 1) Wolff-Kishner reduction utilizes hydrazine, a base, and a high-boiling alcohol solvent to reduce ketone functions to methylene groups. ①+c Dipheny methane 12.23 (a) There are three principal resonance forms of the cyclohexadienyl cation intermediate formed by attack of bromine on p-xylene H Br Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
(h) Anisole is a reactive substrate toward Friedel–Crafts alkylation and yields a mixture of o- and p-benzylated products when treated with benzyl chloride and aluminum chloride. (i) Benzene will undergo acylation with benzoyl chloride and aluminum chloride. ( j) A benzoyl substituent is meta-directing and deactivating. (k) Clemmensen reduction conditions involve treating a ketone with zinc amalgam and concentrated hydrochloric acid. (l) Wolff–Kishner reduction utilizes hydrazine, a base, and a high-boiling alcohol solvent to reduce ketone functions to methylene groups. 12.23 (a) There are three principal resonance forms of the cyclohexadienyl cation intermediate formed by attack of bromine on p-xylene. CH3 H Br CH3 CH3 CH3 CH3 CH3 H Br H Br H2NNH2 KOH diethylene glycol C O Benzophenone Diphenylmethane CH2 Zn(Hg) HCl C O Benzophenone Diphenylmethane CH2 HNO3 H2SO4 C O Benzophenone m-Nitrobenzophenone C O NO2 AlCl3 Benzene CCl O Benzoyl chloride C O Benzophenone AlCl3 CH2Cl Benzyl chloride OCH3 Anisole OCH3 CH2C6H5 o-Benzylanisole OCH3 CH2C6H5 p-Benzylanisole REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 287 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
288 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION Any one of these resonance forms is a satisfactory answer to the question. Because of its ter tiary carbocation character, this carbocation is more stable than the corresponding intermedi- ate formed from benzene (b) Chlorination of m-xylene will give predominantly 4-chloro-1, 3-dimethy benzene CH CH 4- Chloro. More stable clohexadienyl cation The intermediate shown(or any of its resonance forms) is more stable for steric reasons than cyclohexadienyl cation The cyclohexadienyl cation intermediate leading to 4-chloro-1, 3-dimethylbenzene stable and is formed faster than the intermediate leading to chlorobenzene because of it tiary carbocation character more stable than (c) The most stable carbocation intermediate formed during nitration of acetophenone is the one corresponding to meta attack. H CCE H3 CCH more stable than O2 N-Y O2 H NO An acyl group is electron-withdrawing and destabilizes a carbocation to which it is attached. The most stable carbocation intermediate in the nitration of acetophenone is less stable and is formed more slowly than is the corresponding carbocation formed during nitration of less stable than Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
Any one of these resonance forms is a satisfactory answer to the question. Because of its tertiary carbocation character, this carbocation is more stable than the corresponding intermediate formed from benzene. (b) Chlorination of m-xylene will give predominantly 4-chloro-1,3-dimethylbenzene. The intermediate shown (or any of its resonance forms) is more stable for steric reasons than The cyclohexadienyl cation intermediate leading to 4-chloro-1,3-dimethylbenzene is more stable and is formed faster than the intermediate leading to chlorobenzene because of its tertiary carbocation character. (c) The most stable carbocation intermediate formed during nitration of acetophenone is the one corresponding to meta attack. An acyl group is electron-withdrawing and destabilizes a carbocation to which it is attached. The most stable carbocation intermediate in the nitration of acetophenone is less stable and is formed more slowly than is the corresponding carbocation formed during nitration of benzene. CCH3 O H less stable than H NO2 H NO2 CCH3 O CCH3 O CCH3 O H O2N more stable than or H NO2 H NO2 CH3 CH3 H more stable than H Cl H Cl CH3 H Cl CH3 Less stable cyclohexadienyl cation CH3 CH3 m-Xylene CH3 Cl CH3 4-Chloro-1,3- dimethylbenzene CH3 H Cl CH3 More stable cyclohexadienyl cation Cl2 via 288 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website